Some types of pain don’t respond to currently available medicines. Ambros Therapeutics’ in-licensed drug candidate is in pivotal testing for a particular rare type of pain with no FDA-approved therapies, and the biotech will continue developing that program as a public company by merging with Nasdaq-listed Werewolf Therapeutics.
The combined company will keep the Ambros name and operate from that company’s headquarters in San Diego. Along with the all-stock business combination announced Friday, Ambros will be supported by a $150 million private placement expected to support the biotech’s lead molecule up to an FDA submission. The combined company will be led by current Ambros CEO Joseph “Jay” Hagan, who was most recently the chief executive of Regulus Therapeutics, a developer of microRNA-targeting drugs that was acquired by Novartis last year.
Ambros’s lead indication is complex regional pain syndrome type 1 (CRPS-1), a rare disorder in which intense limb pain follows an injury or trauma, such as a bone fracture or surgery. This pain typically presents in phases, the company said in an investor presentation. In the “warm” phase, patients experience redness, swelling, pain, and a feeling of warmth in the six to 12 months following the initial injury. That period is followed by a “cold” phase characterized by severe and persistent pain, vasoconstriction, and discoloration that makes the affected limb look pale or blue. CRPS has two types; type 2 has more involvement of nerve pain. Currently available pain drugs, including opioids, offer limited efficacy for CRPS.
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Ambros’s small molecule, neridronate, belongs to a class of medicines called bisphonates, therapies that treat osteoporosis by preventing bone loss. The company describes neridronate as a differentiated bisphonate. As an intravenously infused drug, more of the main pharmaceutical ingredient is available to offer a therapeutic effect compared to bisphonates formulated as pills, which have more limited bioavailability. Neridronate was initially developed by Italy-based Abiogen Pharma, which steered the drug to approval in its home country in 2016 and sells the product there under the brand name Nerixia. Ambros licensed North American rights to neridronate and holds an option for broader market expansion of the molecule.
In the investor presentation, Ambros said neridronate works by concentrating at the site of the injury during the warm phase. There, the drug reduces bone loss and inflammation. Results from the pivotal studies that supported neridronate’s approval in Italy showed greater than 50% reduction in pain scores and reduced pain intensity compared to a placebo. The drug was well tolerated in clinical testing as well as the commercial setting, where it has been used by more than 600,000 patients.
Ambros aims to succeed where Grünenthal fell short. The German pharmaceutical company licensed rights to neridronate in 2013, but ended up returning them after stopping two Phase 3 studies for futility. In the investor presentation, Ambros said Grünenthal’s studies enrolled CPRS type 1 and type 2 patients with no nuclear imaging to assess bone involvement. Also, most participants were advanced past the warm stage. But there was encouraging data in patients with CRPS-1 who were in the warm stage at baseline.
Ambros’s Phase 3 test is expected to enroll 270 adults with the warm subtype of CRPS-1; preliminary data are expected in 2028. The company said it the FDA has agreed a single Phase 3 trial would be sufficient to support regulatory approval. If the trial readout is positive, Ambros said it could file a new drug application in 2029.
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Going forward, Ambros will focus on neridronate, shelving the cancer assets of Werewolf, which joined the public markets in 2021. The biotech’s cytokine therapies are made with technology that keeps a drug “masked” as it circulates throughout the body, activating the therapy only upon reaching tumors. While the two lead programs yielded encouraging early clinical data, Werewolf’s dwindling cash last year highlighted the urgency of finding a big pharmaceutical partner to continue development of its pipeline. No deals were struck. In February of this year, Werewolf restructured operations and started exploring strategic alternatives for the business.
Ambros launched last December, backed by $125 million in Series A financing led by RA Capital Management and Enavate Sciences. RA Capital will co-lead the private placement with Janus Henderson Investors. Other disclosed investors in this financing include Aberdeen Investments, Adage Capital Partners, ADAR1 Capital Management, Affinity Asset Advisors, Arkin Bio Capital, Balyasny Asset Management, Enavate Sciences, SilverArc Capital, Sphera Healthcare, and Woodline Partners.
The private placement will close concurrent with the close of the business combination, which is expected by the first quarter of 2027. Ambros estimates the proceeds from the deal will last into the first half of 2029. Shareholders of both Ambros and Werewolf still need to approve the merger, which values Ambros at about $500 million. Upon the deal’s close, pre-merger Ambros stockholders will own about 71.7% of the combined company while investors in the private placement hold a 21.5% stake. Pre-merger Werewolf shareholders will own about 6.8% of the combined company. The newly public Ambros is expected to trade on the Nasdaq under the stick symbol “AMBX.”
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